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Health – Genetic defects / Genotoxicity

DNA Properties. Source: wikimedia commons

The genetic make-up of living creatures is found in the cell nucleus (partially in other cell parts). The actual genetic information is stored in the DNA. The DNA is a long chain molecule which looks like a twisted ladder. The rungs of this ladder are made of different building blocks (the four Bases Adenine, Thymine, Guanine und Cytosine). These building blocks code the genetic information. Whilst information in digital computer technology is generated from two symbols (zero and one), four “symbols”, the Bases mentioned above, are in the DNA. A specific sequence of Bases generates genetic information respectively a gene (human beings have about 20,000 genes). Thereby, the number of Bases varies between 10,000 and over one million from gene to gene. One refers to a genetic defect when the sequence of the Bases and/or their links are so changed or damaged that the original function of the cell can no longer be assured. Such gene defects increase with increasing age.

Damage of the genetic make-up

In each cell thousands of chemical changes occur to the DNA every day. The causes are manifold: “own failure” of the DNA mechanism (error in copying the genetic information), thermic collisions with other molecules (in particular with products of the metabolism – the chemically Reactive Oxygen Species (ROS) belong here), or “external” influences such as ionising radiation. The following damages to the bases can occur:

Loss of Bases (in particular Adenine and Guanine. Thousands of these Bases from the DNA of each cell are released per minute).

Changes to the Bases (for example the conversion of Cytosine into Uracil).

Interconnection of Bases (for example the connection of two neighbouring thymine bases under the influence of UV light).

Incorrect sequence of Bases (this occurs with the erroneous copying of the DNA; these so-called replication errors occur very infrequently, perhaps once in every 1,000 million copying activity).

In addition to damage to bases further types of damage can occur or rather cause consequential impairment which is cytogenetically visible:

Individual DNA strand breaks (in the picture of the ladder: break of a holm; the loss of a Base is a frequent cause)

If the chemical modifications were not continually repaired there would be catastrophic results for a living creature. Thus, cells have a highly efficient repair mechanism which identifies errors and damage, and repairs them in a short time. As an example a large number of the identified DNA strand breaks (amongst others individual strand breaks – only 0.5% of all strand breaks are double strand breaks) corrected within the first hour after the appearance of the dysfunction. As a result a weakening of the cell-internal repair mechanism can indirectly increase the number of gene defects in a cell. Uncorrected or incorrectly repaired damage can change or deactivate gene functions and thus, for example, lead to an increased risk of cancer.

Genotoxic damage can be proven with different microbiological methods (Table).

Genotoxicity and health

Examples of validation methods for various genetic and cellular effects. Source: FSM

In addition to the real damage one also needs to keep an eye on the immediate knock-on effects in view of the importance to health. Thereby, the most important effects can be placed on the following list of priorities (1 is less health relevant than 5):

Gene expression: This term refers to the activation of a gene. An activated (expressed) gene forms (synthesises) according genetic information “blueprint” Proteins with defined functions in cell metabolism. Gene damage can suppress or hyperactivate the gene expression. If the precise path of the activation of a specific gene through to reaction in the cell is unknown (today, this is the normal case), then no statements as to their relevance to health can be deduced from the state of the gene expression.

Protein expression: The total of available Proteins in a cell can (in contrast to the total of genes in a cell) vary according to environmental influence and the level of activity of the organism. Changes in the protein composition can indicate health problems. However, the complexity in the interaction of the proteins (human beings have many hundreds of thousands of different Proteins) is so large that, as in the cases of gene expression, universal health statements are rarely possible from protein analysis.

Genotoxic damage (see above): A genotoxic effect as such is not necessarily a risk to health as the majority of DNA damage can be corrected by cell internal repair mechanisms.

Cell cycle: Normally human cells multiply (proliferate) only when they are prompted to do so by signals from other cells, otherwise they remain in a dormant state. Should the proportion of cells in an active phase be increased, this can be an indication of cells on the tumour path.

Apoptosis: this refers to programmed cell mortality. It ensures that cells which are no longer required or which are damaged are destroyed. Disorders in the apoptosis control can have very serious health consequences.

The validation methods for the effects described are compiled in the Table.

Genotoxic electromagnetic radiation

Very high energy (or ionising) radiation (UV-Light, X-rays, radio activity) has been proven to have genotoxic effects. High power high frequency radiation can heat the tissues. Genetic damage can also be caused if the heating effect is large enough. However, the exposure guidelines protect people completely from such dangers. Scientists debate whether genotoxic damage can be caused by low power electromagnetic radiation below the limit values. There is limited evidence in this direction but it is inconsistent and has not been systematically confirmed.

A large European research project, the so-called Reflex Study, has been looking into the topic for several years. As part of the study cell cultures are irradiated in the laboratory and then examined for genotoxicity, gene expression, cell cycle an apoptosis. Overall neither low frequency nor high frequency EMFs have influenced cell cycles, cell growth, cell reproduction or cell mortality. It seems, however, that EMFs with specific signal structures can result in genotoxic effects (strand breaks, Chromosome damage, Micro cores) to particular cell types. The defects, however, are 1) repaired within the cell and do not lead to any noticeable reduction in the cell’s vitality and functionality, and 2) they are minimal in comparison to damage from known genotoxic substances and lay, in part, on the limits of verification of the analysis procedures in use.

A replication study in the context of FSM funding was able to describe the circumstances more precisely. It appears that the increased number of strand breaks only appear in a specific phase of the cell cycle, namely when the cells begin to divide themselves. To do this, the cell cores must duplicate their DNA which, of course, leads to a fragmentation of the DNA. EMFs (in particular low frequency magnetic fields which are switched on and off in a specific rhythm) appear to influence this process of DNA replication but do not directly damage the genotype.

Conclusions

Today it can be said that it is most unlikely that weak EMFs can damage the DNA whereas there are indications that specific signals can influence the molecular processes in the replication phase of the cell cycle. The functionality and vitality of the cells are not affected thereby. The processes and mechanisms involved are not yet known in detail and require further investigation.

Glossar

The Swiss Research Foundation for Electricity and Mobile Communication (FSM) is a non-profit-making foundation with the purpose of promoting scientific research into the chances and risks of radio and electric power technologies that produce and use electromagnetic fields.